The form of molecules to return: A Q&A on designing DNA nanostructures for biomedical purposes – Uplaza

By discovering new methods to control matter on the atomic and molecular ranges, advances in nanotechnology are paving the way in which for improvements in medication, electronics, supplies science and environmental remediation, amongst many different areas.

An essential specialty on this discipline—and a signature space of examine on the College at Albany’s RNA Institute—is DNA nanotechnology, whereby the bottom pairs that comprise DNA molecules are manipulated to construct tiny buildings in numerous shapes that can be utilized for purposes together with drug supply, medical diagnostics and even information storage.

RNA Institute researchers together with Postdoctoral Fellow Bharath Raj Madhanagopal and Senior Analysis Scientist Arun Richard Chandrasekaran, along with a crew of UAlbany collaborators, coauthored a brand new examine that explored the distinctive properties of a sure sort of DNA nanostructure referred to as “switchback DNA” that would have implications for DNA folding in nature and be helpful in designing new forms of nanostructures with biomedical purposes.

Their findings had been printed in Nature Communications.

Right here, Madhanagopal and Chandrasekaran share insights on the basics of their discipline and the advances that lie in wait with new discoveries in DNA nanotechnology.

What are DNA nanostructures, and why are they essential?

Many know DNA because the molecule that shops the genetic data that’s handed from one era to the subsequent. The chemical properties of DNA that make it a wonderful molecule for storing genetic data additionally make it a helpful building materials—particularly in the case of making tiny objects, as small as just a few nanometers.

The sequences of the 4 nucleobases in DNA—adenine, guanine, thymine, and cytosine –are inherently programmable. It is because adenine at all times pairs with thymine, and guanine with cytosine. These dependable patterns in base pairing enable us to design particular strands of DNA that bind collectively like Lego blocks to kind nanostructures.

By utilizing DNA to construct nanostructures, we will obtain wonderful precision within the measurement of the buildings. We will additionally make objects of numerous shapes and architectural intricacies—capabilities that aren’t simply achieved utilizing different applied sciences. DNA nanostructures at the moment are being developed to be used in drug supply, diagnostics, and information storage, to call just a few purposes.

What’s ‘switchback DNA?’

Simply as we use bricks to assemble buildings, we use nanometer-sized constructing blocks referred to as “motifs” and “tiles” product of DNA to create elaborate buildings in DNA nanotechnology. Much like how bricks can come in numerous styles and sizes, so can motifs and tiles. Creating these structural motifs and understanding their properties is the inspiration of DNA nanotechnology analysis.

“Switchback DNA” is among the earliest DNA motifs designed by Nadrian Seeman, the founding father of the sector of DNA nanotechnology. We wished to discover how its curious structural options would manifest in nanostructures. By learning the properties of switchback DNA, we imagine we will create much more numerous DNA-based nano-objects with unique properties.

What makes switchback DNA distinctive?

Switchback DNA has solely two strands, so it may be immediately in contrast with the double helical construction of DNA that everybody is acquainted with. In switchback DNA, the 2 strands have sections, referred to as half-turns, that resemble regular DNA, however the way in which they’re organized makes switchback DNA distinctive.

Usually, DNA is a double helix with right-handed helical sense all through the molecule. In switchback DNA, right-handed half-turns are organized in such a method that the molecule as a complete is a left-handed double helix. It is because in the event you hint the spine of DNA alongside the helix, you will see that that after each half-turn, the strands fold again. These variations are illustrated within the diagram beneath.

We now have discovered that switchback DNA’s distinctive construction can have an effect on properties essential to its potential function in biomedical purposes—issues like structural stability, vulnerability to enzymes, and immunogenic properties, which, for instance, can affect the power of a nanostructure to successfully ship a drug to a specific tissue. Understanding these properties, and determining which may be managed and find out how to management them, is important.

What does the sector stand to realize by higher understanding switchback DNA?

The outcomes of this examine will assist researchers who make DNA nanostructures enhance their designs utilizing switchback DNA constructing blocks.

For instance, we now know {that a} frequent enzyme referred to as “DNase I” doesn’t degrade switchback DNA as shortly because it degrades standard B-DNA (the DNA that’s typically present in residing organisms). If we wish to use DNA nanostructures to hold medication to tissues within the physique, we do not need an enzyme to interrupt down the nanostructure earlier than it may attain the goal tissue.

If this occurred, the drug wouldn’t be efficient. We will now contemplate incorporating switchback DNA to assist mitigate this problem, which is a standard roadblock within the discipline.

We additionally discovered that there are genetic sequences within the human genome that may doubtlessly fold into switchback DNA. Our outcomes recommend that below some circumstances, DNA with particular repeating patterns might kind switchback DNA. These sequences are prevalent within the chromosomes of animals and vegetation, and may undertake structural kinds about which we all know little or no.

It’s thrilling to know that these sequences can fold into switchback DNA in a take a look at tube below sure circumstances. Whether or not this may occur in a residing cell stays to be seen.

As a result of these repetitive sequences are concerned in ailments similar to myotonic dystrophy and Huntington’s illness, this avenue of examine could assist us higher perceive this class of ailments, and it might additionally assist us uncover new drug targets for these ailments sooner or later.

What are the largest takeaways from this work?

Our work with switchback DNA reveals that we will “tune” the properties of DNA by folding it into completely different patterns with out chemical modifications. Understanding the properties of switchback DNA will likely be helpful in creating DNA units for biosensing, drug supply, DNA computation and different purposes.

Our findings additionally exhibit that the foundations of complementarity that Watson and Crick outlined of their iconic double-helical mannequin of DNA construction must be expanded. Within the mannequin proposed by Watson and Crick, the instructions of the 2 strands are reverse. Which means one finish of the primary strand interacts with the alternative finish of the second strand.

In switchback DNA, the bottom pairing sample is completely different. Whereas many of the guidelines of complementarity outlined by Watson and Crick apply to switchback DNA, the place of the bottom pairs differs.

Lastly, our speculation that repeat sequences might kind switchback DNA buildings opens up fascinating discussions—and future research—on the organic prevalence of such non-traditional DNA buildings.